Alterations In Posttraumatic Stress Disorder Research Articles

Attention, attention! Posttraumatic stress disorder is associated with altered attention-related brain function.

Posttraumatic stress disorder (PTSD) is a debilitating condition characterized by altered arousal, mood, and cognition. Studies report attentional alterations such as threat bias in individuals with PTSD, though this work has largely been conducted within emotionally-charged contexts (e.g., threatening stimuli). Emerging behavioral evidence suggests that PTSD-related attention deficits exist even in the absence of threatening cues or anxiety triggers. However, the role and functioning of attention brain circuits as they relate to PTSD remains underexplored. In this mini review, we highlight recent work using non-emotional stimuli to investigate the neurobiology of attention and disruptions to attention-related brain function among individuals with PTSD. We then discuss gaps in the current literature, including questions pertaining to the neural circuitry of attentional alterations in PTSD, as well as the contributions that trauma exposure, PTSD symptoms, comorbidities, and pre-existing vulnerabilities may have in this relationship. Finally, we suggest future directions for this emerging area of research, which may further inform knowledge surrounding the neurobiological underpinnings of PTSD and potential treatments.

[Memory alterations in post-traumatic stress disorder].

Post-Traumatic Stress Disorder (PTSD) is a disorder that develops following the experience of a highly stressful event, which involves a confrontation with death or the threat of death, serious injury or sexual violence. It is characterized by symptoms such as intrusions, avoidance and hypervigilance. According to the literature, PTSD is associated with an imbalance between a privileged memorization of the emotional and sensory aspects of the traumatic event and a failure to memorize the contextual aspects. That is why PTSD is now considered a memory disorder whose effects extend to several components. In this review article, we focus on how PTSD affects long-term memory. The first part describes the long-term effects of PTSD on episodic memory with emphasis on the difficulties in encoding certain elements of the traumatic event and their consequences. These difficulties may be manifested in the narration of the trauma, with a discourse of the traumatic event lacking in contextual details. They may also lead to reliving and generalizing the fear to other contexts, whether they are related to the trauma or not. The second part of the article discusses how PTSD affects autobiographical memory and has consequences for the construction of identity and the perception of the past, present and future of people with this disorder. Autobiographical memory, which plays a key role in the storage of past personal memories as well as in identity formation, shows several forms of disruption induced by PTSD. First, a decrease in contextual details associated with memories of the personal past is observed, meaning that people with PTSD tend to remember their past experiences less accurately. Second, a propensity to project the future in a more negative and unpredictable manner is evidenced, related to a feeling of uncertainty about the future in PTSD suffering individuals. Finally, alterations in the encoding of present events due to the disruptive effects of post-traumatic stress symptoms during the encoding process are also identified.

The influence of sleep on fear extinction in trauma-related disorders

In Posttraumatic Stress Disorder (PTSD), fear and anxiety become dysregulated following psychologically traumatic events. Regulation of fear and anxiety involves both high-level cognitive processes such as cognitive reattribution and low-level, partially automatic memory processes such as fear extinction, safety learning and habituation. These latter processes are believed to be deficient in PTSD. While insomnia and nightmares are characteristic symptoms of existing PTSD, abundant recent evidence suggests that sleep disruption prior to and acute sleep disturbance following traumatic events both can predispose an individual to develop PTSD. Sleep promotes consolidation in multiple memory systems and is believed to also do so for low-level emotion-regulatory memory processes. Consequently sleep disruption may contribute to the etiology of PTSD by interfering with consolidation in low-level emotion-regulatory memory systems. During the first weeks following a traumatic event, when in the course of everyday life resilient individuals begin to acquire and consolidate these low-level emotion-regulatory memories, those who will develop PTSD symptoms may fail to do so. This deficit may, in part, result from alterations of sleep that interfere with their consolidation, such as REM fragmentation, that have also been found to presage later PTSD symptoms. Here, sleep disruption in PTSD as well as fear extinction, safety learning and habituation and their known alterations in PTSD are first briefly reviewed. Then neural processes that occur during the early post-trauma period that might impede low-level emotion regulatory processes through alterations of sleep quality and physiology will be considered. Lastly, recent neuroimaging evidence from a fear conditioning and extinction paradigm in patient groups and their controls will be considered along with one possible neural process that may contribute to a vulnerability to PTSD following trauma.

Spectral decomposition of EEG microstates in post-traumatic stress disorder

Microstates offer a promising framework to study fast-scale brain dynamics in the resting-state electroencephalogram (EEG). However, microstate dynamics have yet to be investigated in post-traumatic stress disorder (PTSD), despite research demonstrating resting-state alterations in PTSD. We performed microstate-based segmentation of resting-state EEG in a clinical population of participants with PTSD (N = 61) and a non-traumatized, healthy control group (N = 61). Microstate-based measures (i.e., occurrence, mean duration, time coverage) were compared group-wise using broadband (1–30 Hz) and frequency-specific (i.e., delta, theta, alpha, beta bands) decompositions. In the broadband comparisons, the centro-posterior maximum microstate (map E) occurred significantly less frequently (d = -0.64, pFWE = 0.03) and had a significantly shorter mean duration in participants with PTSD as compared to controls (d = -0.71, pFWE < 0.01). These differences were reflected in the narrow frequency bands as well, with lower frequency bands like delta (d = -0.78, pFWE < 0.01), theta (d = -0.74, pFWE = 0.01), and alpha (d = -0.65, pFWE = 0.02) repeating these group-level trends, only with larger effect sizes. Interestingly, a support vector machine classification analysis comparing broadband and frequency-specific measures revealed that models containing only alpha band features significantly out-perform broadband models. When classifying PTSD, the classification accuracy was 76 % and 65 % for the alpha band and the broadband model, respectively (p = 0.03). Taken together, we provide original evidence supporting the clinical utility of microstates as diagnostic markers of PTSD and demonstrate that filtering EEG into distinct frequency bands significantly improves microstate-based classification of a psychiatric disorder.

Regional specificity and clinical correlates of cortical GABA alterations in posttraumatic stress disorder.

Gamma-aminobutyric acid (GABA) metabolism is implicated in posttraumatic stress disorder (PTSD) and may be altered in prefrontal-limbic brain regions involved in arousal regulation. This study used proton magnetic resonance spectroscopy (MRS) to test the hypothesis that PTSD and trauma-exposed non-PTSD comparison (TENC) adults have significantly different GABA than healthy comparison (HC) subjects in two brain areas implicated in arousal (medial prefrontal cortex, insula) but not in a control brain area (posterior temporal cortex). We also examined whether GABA alterations correlated with hyperarousal and dissociation symptoms. One hundred and fourteen participants (39 PTSD, 34 TENC, 41 HC) underwent 3T MRS of the medial prefrontal, right insular, and right posterior temporal cortices, and the GABA plus macromolecule signal (GABA+) was normalized to creatine (Cr). The Clinician Administered PTSD Scale measured hyperarousal symptoms, including sleep disruption. The Dissociative Experiences Scale assessed dissociation symptoms. PTSD and TENC participants had significantly lower mPFC GABA+/Cr than HC participants, and this deficit was significantly correlated with greater dissociation. Compared with HC, PTSD patients but not TENC had significantly lower insula GABA+/Cr. Total hyperarousal symptoms and sleep disruption were not significantly associated with GABA+/Cr alterations in either region. Our findings point to lower GABA in cortical areas implicated in arousal regulation in PTSD and suggest that GABA alterations are associated with symptoms of trauma-related psychopathology but not always a biomarker of diagnosis. These findings also add to evidence that dissociation has distinct neural correlates within PTSD, including high excitability of medial prefrontal cortex.

The Molecular Biology of Susceptibility to Post-Traumatic Stress Disorder: Highlights of Epigenetics and Epigenomics

Exposure to trauma is one of the most important and prevalent risk factors for mental and physical ill-health. Excessive or prolonged stress exposure increases the risk of a wide variety of mental and physical symptoms. However, people differ strikingly in their susceptibility to develop signs and symptoms of mental illness after traumatic stress. Post-traumatic stress disorder (PTSD) is a debilitating disorder affecting approximately 8% of the world’s population during their lifetime, and typically develops after exposure to a traumatic event. Despite that exposure to potentially traumatizing events occurs in a large proportion of the general population, about 80–90% of trauma-exposed individuals do not develop PTSD, suggesting an inter-individual difference in vulnerability to PTSD. While the biological mechanisms underlying this differential susceptibility are unknown, epigenetic changes have been proposed to underlie the relationship between exposure to traumatic stress and the susceptibility to develop PTSD. Epigenetic mechanisms refer to environmentally sensitive modifications to DNA and RNA molecules that regulate gene transcription without altering the genetic sequence itself. In this review, we provide an overview of various molecular biological, biochemical and physiological alterations in PTSD, focusing on changes at the genomic and epigenomic level. Finally, we will discuss how current knowledge may aid us in early detection and improved management of PTSD patients.

A randomized, double-blind, placebo-controlled trial of hydrocortisone augmentation of Prolonged Exposure for PTSD in U.S. combat veterans

ObjectiveCognitive behavioral therapies such as Prolonged Exposure (PE) are considered first line treatments for posttraumatic stress disorder (PTSD). Nonetheless, many continue to experience significant symptoms following treatment and there is interest in enhancing treatment effectiveness. Glucocorticoid alterations in PTSD are well documented, and these steroids have been shown to enhance extinction learning. MethodsAugmentation of PE with the synthetic glucocorticoid hydrocortisone (HCORT) was tested in a randomized, double-blind, placebo-controlled trial in 60 veterans of wars in Iraq or Afghanistan with PTSD (NCT01525680). Participants ingested 30 mg oral HCORT or placebo 30 min prior to exposure sessions. Primary outcome measure: PTSD severity assessed by the CAPS; secondary outcome measures: self reported PTSD symptoms assessed by the PDS and depression assessed by the BDI; all administered at pretreatment, posttreatment, and 3-month follow up. ResultsAcross conditions, there was a robust effect of PE over time. An intent-to-treat analysis showed that HCORT did not measurably improve PTSD symptoms or secondary outcomes. However, exploratory analyses indicated that veterans with mild TBI exposure and current postconcussive symptoms showed a greater reduction in hyperarousal symptoms following PE treatment with HCORT augmentation. Additionally, veterans with higher baseline glucocorticoid sensitivity showed a greater reduction in avoidance symptoms with HCORT augmentation. ConclusionsTreatment matching based on cognitive or biological vulnerabilities might lead to greater efficacy of PE with glucocorticoid augmentation.

Mechanisms Underlying Unconscious Processing and Their Alterations in Post-traumatic Stress Disorder: Neuroimaging of Zero Monetary Outcomes Contextually Framed as "No Losses" vs. "No Gains".

Although unconscious processing is a key element of mental operation, its neural correlates have not been established. Also, clinical observations suggest that unconscious processing may be involved in the pathophysiology of post-traumatic stress disorder (PTSD), but the neurobiological mechanisms underlying such impairments remain unknown. The purpose of the present study was to examine putative mechanisms underlying unconscious processing by healthy participants and to determine whether these mechanisms may be altered in PTSD patients. Twenty patients with PTSD and 27 healthy individuals were administered a validated wheel of fortune-type gambling task during functional magnetic resonance imaging (fMRI). Unconscious processing was elicited using unconscious contextual framing of the zero monetary outcomes as “no loss,” “no gain” or as “neutral.” Brief passive visual processing of the “no loss” vs. “no gain” contrast by healthy participants yielded bilateral frontal-, temporal- and insular cortices and striatal activations. Between-group comparison revealed smaller activity in the left anterior prefrontal-, left dorsolateral prefrontal-, right temporal- and right insular cortices and in bilateral striatum in PTSD patients with the left dorsolateral prefrontal cortex activity been more pronounced in those with greater PTSD severity. These observations implicate frontal-, temporal-, and insular cortices along with the striatum in the putative mechanisms underlying unconscious processing of the monetary outcomes. Additionally, our results support the hypothesis that PTSD is associated with primary cortical and subcortical alterations involved in the above processes and that these alterations may be related to some aspects of PTSD symptomatology.

Altered dynamic parahippocampus functional connectivity in patients with post-traumatic stress disorder

Objectives This study investigated dynamic brain functional alterations in post-traumatic stress disorder (PTSD) patients with resting state functional magnetic resonance imaging. Methods Degree centrality (DC) and seed-based functional connectivity (FC) analyses were conducted among typhoon survivours with (n = 27) and without PTSD (n = 33) and healthy controls (HC) (n = 30) to assess the intrinsic dysconnectivity pattern and network-level brain function. Results Both the PTSD group and the trauma-exposed control (TEC) group had increased DC in the left parahippocampal gyrus relative to the HC group. More increased DC in the left parahippocampal gyrus was found in the PTSD group. Both traumatised groups exhibited decreased left parahippocampal gyrus dynamic FC with the bilateral middle frontal gyrus and superior frontal gyrus relative to the HC group. The Checklist-Civilian Version score was positively correlated with dynamic FC between the parahippocampal gyrus and left superior frontal gyrus but was negatively correlated with dynamic FC between the parahippocampal gyrus and right middle frontal gyrus. Conclusions Trauma exposure may lead to an altered dynamic FC in individuals with or without PTSD. An altered DC in the parahippocampal gyrus may be an important risk factor for PTSD development following trauma exposure. A more prominently increased DC in the parahippocampal gyrus might be a common trait in the PTSD group.

Immune biomarkers alterations in post-traumatic stress disorder: A systematic review and meta-analysis

Background: Studies have reported the changes of immune biomakers in post-traumatic stress disorder (PTSD), but the results were conflicting. Our aim was to investigate the changes of immune biomarkers in PTSD. Methods: Literatures investigating the changes of immune markers in PTSD published in English were systematically searched through PubMed, Embase and Web of Science. We conducted random effects meta-analyses relating PTSD to immune biomarker concentrations and using subgroup analyses to resolve heterogeneity. Results: A total of 2606 articles were screened and 42 samples were included by the systematic review. The levels of interleukin-1β (IL-1β, P = 0.01), IL-2 (P = 0.006), IL-6 (P = 0.0002), interferon-γ (IFN-γ, P = 0.004), tumor necrosis factor-α (TNF-α, P = 0.004), C-reactive protein (CRP, P = 0.0003) and white blood cell (WBC, P = 0.01) were higher in PTSD than healthy controls (HC). Subgroup meta-analyses for psychotropic medication showed the levels of IL-1β and IL-2 were not increased in the PTSD. Subgroup meta-analyses for whether HC exposed to trauma showed the levels of IL-1β and IL-6 were not increased in the PTSD. Egger´s test revealed there was no publication bias. However, there was significant heterogeneity across studies for immune markers other than for WBC (P = 0.14, I2 = 45%). Subgroup analyses based on sex, HC exposed to trauma, PTSD comorbid major depressive disorder, PTSD on psychotropic medications partially or completely resolved heterogeneity for some immune biomarkers. Conclusion: This meta-analysis provides evidence for elevation of IFN-γ, TNF-α, CRP, and WBC in PTSD.

Childhood maltreatment experiences are associated with altered diffusion in occipito-temporal white matter pathways.

BackgroundChildhood maltreatment may contribute to brain alterations in posttraumatic stress disorder (PTSD). We previously found that PTSD was associated with white matter compromise, or lower fractional anisotropy (FA), in the left inferior longitudinal fasciculus (ILF). In this study, including non‐PTSD controls, we examined whether ILF FA was associated with maltreatment exposures, including those that meet DSM‐IV criterion A (physical abuse, sexual abuse) and those that typically do not (emotional abuse, emotional neglect, physical neglect). We hypothesized that lower FA would be associated with PTSD diagnosis and with both categories of maltreatment.MethodsNinety‐three participants (51 female), ages 20–50, were enrolled, including 32 with lifetime DSM‐IV PTSD, 27 trauma‐exposed non‐PTSD controls, and 34 healthy controls. Participants completed structured interviews, the Childhood Trauma Questionnaire (CTQ), and diffusion‐weighted imaging (36 directions). Probabilistic tractography (using FreeSurfer's TRACULA) was used to assess diffusion metrics in the ILF.ResultsContrary to our hypothesis, there was no significant effect of diagnostic group on FA. In contrast, higher CTQ scores were significantly associated with lower FA in the ILF bilaterally. This association of maltreatment with lower FA remained statistically significant after controlling for diagnostic group, and it was significant for both criterion‐A‐type and noncriterion‐A‐type maltreatment categories.ConclusionsThis work contributes to a growing body of literature indicating that different forms of childhood maltreatment are associated with altered white matter microstructure in the ILF, an association pathway involved in integrating visual information from occipital regions with emotion processing functions of the anterior temporal lobe.

The Role of Proopiomelanocortin and α-Melanocyte-Stimulating Hormone in the Metabolic Syndrome in Psychiatric Disorders: A Narrative Mini-Review.

The metabolic syndrome (MetS) comprises abdominal obesity, preclinical or full diabetes type 2, arterial hypertension, and dyslipidemia and affects a significant proportion of the general population with a remarkably higher prevalence in patients suffering from psychiatric disorders. However, studies exploring the pathogenetic link between MetS and psychiatric diseases are rare. Here, we aim to narrow this gap in knowledge by providing a narrative review on this topic that focuses on two psychiatric diseases, namely on schizophrenia and posttraumatic stress disorder (PTSD) since we assume them to be associated with two different main causalities of MetS: in schizophrenia, MetS evidently develops or aggravates in response to antipsychotic drug treatment while it assumingly develops in response to stress-induced endocrine and/or epigenetic alterations in PTSD. First, we compared the prevalences of MetS and associated pathologies (which we took from the latest meta-analyses) among different psychiatric disorders and were surprised that the prevalences of arterial hypertension and hyperglycemia in PTSD almost doubles those of the other psychiatric disorders. Next, we performed a literature search on the neurobiology of MetS and found numerous articles describing a role for proopiomelanocortin (POMC) in MetS. Thus, we concentrated further analysis on POMC and one of its downstream effector hormones, α-melanocyte-stimulating hormone (α-MSH). We found some evidence for a role of POMC in both PTSD and schizophrenia, in particular in antipsychotic-induced MetS, as well as for α-MSH in schizophrenia, but, surprisingly, no study on α-MSH in PTSD. Taken together, our synopsis reveals, first, a potential interaction between the POMC system and stress in the assumingly at least partially shared pathogenesis of psychiatric disorders and MetS, second, that modulation of the POMC system, in particular of the melanocortin 3 and 4 receptors, might be a promising target for the treatment of MetS and, third, that the DNA methylation status of POMC might speculatively be a promising biomarker for MetS in general and, possibly, in particular in the context of stress-related psychiatric conditions such as PTSD. To best of our knowledge, this is the first review on the role of the POMC system in MetS in psychiatric disorders.

Glucocorticoids and Hippocampal Structure and Function in PTSD.

This review examines the putative link between glucocorticoid and hippocampal abnormalities in posttraumatic stress disorder (PTSD). Increased glucocorticoid receptor (GR) sensitivity in PTSD may permit enhanced negative feedback inhibition of cortisol at the pituitary, hypothalamus, or other brain regions comprising the hypothalamic-pituitary-adrenal (HPA) axis and would be expected to affect other physiological systems that are regulated by glucocorticoids. Molecular and transcriptional studies of cortisol are consistent with the hypothesis that cortisol actions may be amplified in PTSD as a result of enhanced GR sensitivity in monocytes and some brain regions, although cortisol levels themselves are unchanged and oftentimes lower than normal. Concurrently, magnetic resonance imaging studies have demonstrated that individuals with PTSD have smaller hippocampal volume than individuals without PTSD. Initial hypotheses regarding the mechanism underlying hippocampal alterations in PTSD focused on elevated glucocorticoid levels in combination with extreme stress as the primary cause, but this explanation has not been well supported in human studies. Lack of data from neuroimaging studies preclude a firm link between PTSD onset and hippocampal volume changes. Rather, the available evidence is consistent with the possibility that smaller hippocampal volume (like reduced cortisol levels and enhanced GR sensitivity) may be a vulnerability factor for developing the disorder; limitations of hippocampal-based models of PTSD are described. We further review neuroimaging studies examining hippocampal structure and function following manipulation of glucocorticoid levels and also examining changes in the hippocampus in relationship to other brain regions. Evidence that the GR may be an important therapeutic target for the treatment of PTSD, especially for functions subserved by the hippocampus, is discussed. Implications of the current review for future research are described, with an emphasis on the need to integrate findings of glucocorticoid abnormalities with functional-imaging paradigms to formulate a comprehensive model of HPA-axis functioning in PTSD.

Cerebellar and Prefrontal Cortical Alterations in PTSD: Structural and Functional Evidence

Background Neuroimaging studies have revealed that disturbances in network organization of key brain regions may underlie cognitive and emotional dysfunction in posttraumatic stress disorder (PTSD). Examining both brain structure and function in the same population may further our understanding of network alterations in PTSD. Methods We used tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and functional connectivity in unmedicated individuals with PTSD (n = 21) and healthy comparison participants (n = 18). These regions were then used as seeds for follow-up anatomical covariance and functional connectivity analyses. Results Smaller volume in the cerebellum and weaker structural covariance between the cerebellum seed and the middle temporal gyrus were observed in the PTSD group. Individuals with PTSD also exhibited lower whole-brain connectivity in the cerebellum, dorsolateral prefrontal cortex (dlPFC) and medial prefrontal cortex. Functional connectivity in the cerebellum and grey matter volume in the dlPFC were negatively correlated with PTSD severity as measured by the DSM-5 PTSD Checklist (PCL-5; r = −.0.77, r = − 0.79). Finally, seed connectivity revealed weaker connectivity within nodes of the central executive network (right and left dlPFC), and between nodes of the default mode network (medial prefrontal cortex and cerebellum) and the supramarginal gyrus, in the PTSD group. Conclusion We demonstrate structural and functional alterations in PTSD converging on the PFC and cerebellum. Whilst PFC alterations are relatively well established in PTSD, the cerebellum has not generally been considered a key region in PTSD. Our findings add to a growing evidence base implicating cerebellar involvement in the pathophysiology of PTSD.

Generalisation of fear in PTSD related to prolonged childhood maltreatment: an experimental study.

Fear responses are particularly intense and persistent in post-traumatic stress disorder (PTSD), and can be evoked by unspecific cues that resemble the original traumatic event. Overgeneralisation of fear might be one of the underlying mechanisms. We investigated the generalisation and discrimination of fear in individuals with and without PTSD related to prolonged childhood maltreatment. Sixty trauma-exposed women with (N = 30) and without (N = 30) PTSD and 30 healthy control participants (HC) underwent a fear conditioning and generalisation paradigm. In a contingency learning procedure, one of two circles of different sizes was associated with an electrical shock (danger cue), while the other circle represented a safety cue. During generalisation testing, online risk ratings, reaction times and fear-potentiated startle were measured in response to safety and danger cues as well as to eight generalisation stimuli, i.e. circles of parametrically varying size creating a continuum of similarity between the danger and safety cue. The increase in reaction times from the safety cue across the different generalisation classes to the danger cue was less pronounced in PTSD compared with HC. Moreover, PTSD participants expected higher risk of an aversive event independent of stimulus types and task. Alterations in generalisation constitute one part of fear memory alterations in PTSD. Neither the accuracy of a risk judgement nor the strength of the induced fear was affected. Instead, processing times as an index of uncertainty during risk judgements suggested a reduced differentiation between safety and threat in PTSD.

White matter integrity alterations in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating condition which can develop after exposure to traumatic stressors. Seventy-five adults were recruited from the community, 25 diagnosed with PTSD along with 25 healthy and 25 trauma-exposed age- and gender-matched controls. Participants underwent clinical assessment and magnetic resonance imaging. A previous voxel based morphometry (VBM) study using the same subject cohort identified decreased grey matter (GM) volumes within frontal/subcortical brain regions including the hippocampus, amygdala, and anterior cingulate cortex (ACC). This study examines the microstructural integrity of white matter (WM) tracts connecting the aforementioned regions/structures. Using diffusion tensor imaging, we investigated the integrity of frontal/subcortical WM tracts between all three subject groups. Trauma exposed subjects with and without PTSD diagnosis were identified to have significant disruption in WM integrity as indexed by decreased fractional anisotropy (FA) in the uncinate fasciculus (UF), cingulum cingulate gyrus (CCG), and corpus callosum (CC), when compared with healthy non-trauma-exposed controls. Significant negative correlations were found between total Clinician Administered PTSD scale (CAPS) lifetime clinical subscores and FA values of PTSD subjects in the right UF, CCG, CC body, and right superior longitudinal fasciculus (SLF). An analysis between UF and SLF FA values and VBM determined rostral ACC GM values found a negative correlation in PTSD subjects. Findings suggest that compromised WM integrity in important tracts connecting limbic structures such as the amygdala to frontal regions including the ACC (i.e., the UF and CCG) may contribute to impairments in threat/fear processing associated with PTSD.

Automated measurement of hippocampal subfields in PTSD: Evidence for smaller dentate gyrus volume

Smaller hippocampal volume has been consistently observed as a biomarker of posttraumatic stress disorder (PTSD). However, less is known about individual volumes of the subfields composing the hippocampus such as the dentate gyrus and cornu ammonis (CA) fields 1–4 in PTSD. The aim of the present study was to examine the hypothesis that volume of the dentate gyrus, a region putatively involved in distinctive encoding of similar events, is smaller in individuals with PTSD versus trauma-exposed controls. Ninety-seven recent war veterans underwent structural imaging on a 3T scanner and were assessed for PTSD using the Clinician-Administered PTSD Scale. The hippocampal subfield automated segmentation program available through FreeSurfer was used to segment the CA4/dentate gyrus, CA1, CA2/3, presubiculum, and subiculum of the hippocampus. Results showed that CA4/dentate gyrus subfield volume was significantly smaller in veterans with PTSD and scaled inversely with PTSD symptom severity. These results support the view that dentate gyrus abnormalities are associated with symptoms of PTSD, although additional evidence is necessary to determine whether these abnormalities underlie fear generalization and other memory alterations in PTSD.

Grey matter density changes of structures involved in Posttraumatic Stress Disorder (PTSD) after recovery following Eye Movement Desensitization and Reprocessing (EMDR) therapy

Recovery of stress-induced structural alterations in Posttraumatic Stress Disorder (PTSD) remains largely unexplored. This study aimed to determine whether symptoms improvement is associated with grey matter (GM) density changes of brain structures involved in PTSD. Two groups of PTSD patients were involved in this study. The first group was treated with Eye Movement Desensitization and Reprocessing (EMDR) therapy and recovered from their symptoms (recovery group) (n = 11); Patients were scanned prior to therapy (T1), one week (T2) and five months after the end of therapy (T3). The second group included patients which followed a supportive therapy and remained symptomatic (wait-list group) (n = 7). They were scanned at three time-steps mimicking the same inter-scan intervals. Voxel-based morphometry (VBM) was used to characterize GM density evolution. GM density values showed a significant group-by-time interaction effect between T1 and T3 in prefrontal cortex areas. These interaction effects were driven by a GM density increase in the recovery group with respect to the wait-list group. Symptoms removal goes hand-in-hand with GM density enhancement of structures involved in emotional regulation.

Combat Exposure Severity Is Associated With Reduced Cortical Thickness in Combat Veterans: A Preliminary Report

Background Chronic stress and related physiological responses are known to have deleterious effects on neural integrity. Combat exposure is a notoriously pathogenic stressor, and with over 2 million U.S. troops deployed to active combat zones since 2001, there is an urgent need to advance our understanding of its potential neural impact. Previous evidence suggests structural alterations in posttraumatic stress disorder (PTSD) and more recent studies have explored cortical thinning specifically. This preliminary study investigates the impact of combat exposure on cortical thickness, controlling for history of early life stress and age. Methods Twenty-one combat-exposed Veterans with PTSD and 20 non-PTSD combat-exposed controls (mean age 32.7) completed the Combat Exposure Scale, Childhood Trauma Questionnaire, and structural magnetic resonance imaging in a Siemens 3T TIM trio system. General linear model was used to examine the effect of combat exposure on cortical thickness, controlling for early life trauma exposure and age using cluster-wise correction (p < 0.05). Results This preliminary study found a negative correlation between combat exposure severity (CES) and cortical thickness in the left superior temporal and left rostral middle frontal regions, as well as an interaction between PTSD diagnosis status and CES, in the superior temporal/insular region showing a stronger negative correlation between CES and cortical thickness in the non-PTSD group. Conclusions Though caution should be taken with interpretation given the preliminary nature of the findings, the results indicate combat exposure may affect cortical structure beyond possible alterations due to early life stress exposure or PTSD psychopathology. Though replication in larger samples is required, these results provide useful information regarding possible neural biomarkers and treatment targets for combat-related psychopathology as well as highlighting the pathogenic effects of combat.

Hemodynamic variability in soldiers with trauma: Implications for functional MRI connectivity studies.

Functional MRI (fMRI) is an indirect measure of neural activity as a result of the convolution of the hemodynamic response function (HRF) and latent (unmeasured) neural activity. Recent studies have shown variability of HRF across brain regions (intra-subject spatial variability) and between subjects (inter-subject variability). Ignoring this HRF variability during data analysis could impair the reliability of such fMRI results. Using whole-brain resting-state fMRI (rs-fMRI), we employed hemodynamic deconvolution to estimate voxel-wise HRF. Studying the impact of mental disorders on HRF variability, we identified HRF aberrations in soldiers (N = 87) with posttraumatic stress disorder (PTSD) and mild-traumatic brain injury (mTBI) compared to combat controls. Certain subcortical and default-mode regions were found to have significant HRF aberrations in the clinical groups. These brain regions have been previously associated with neurochemical alterations in PTSD, which are known to impact the shape of the HRF. We followed-up these findings with seed-based functional connectivity (FC) analysis using regions-of-interest (ROIs) whose HRFs differed between the groups. We found that part of the connectivity group differences reported from traditional FC analysis (no deconvolution) were attributable to HRF variability. These findings raise the question of the degree of reliability of findings from conventional rs-fMRI studies (especially in psychiatric populations like PTSD and mTBI), which are corrupted by HRF variability. We also report and discus, for the first time, voxel-level HRF alterations in PTSD and mTBI. To the best of our knowledge, this is the first study to report evidence for the impact of HRF variability on connectivity group differences. Our work has implications for rs-fMRI connectivity studies. We encourage researchers to incorporate hemodynamic deconvolution during pre-processing to minimize the impact of HRF variability.